Neutrophils in Tuberculosis: Cell Biology,Cellular Networking and Multitasking in Host Defense

Neutrophils readily infiltrate infection foci, phagocytose and usually destroy microbes. In tuberculosis (TB), a chronic pulmonary infection caused by Mycobacterium tuberculosis (Mtb), neutrophils harbor bacilli, are abundant in tissue lesions, and their abundances in blood correlate with poor disease outcomes in patients. The biology of these innate immune cells in TB is complex. Neutrophils have been assigned host-beneficial as well as deleterious roles. The short lifespan of neutrophils purified from blood poses challenges to cell biology studies, leaving intracellular biological processes and the precise consequences of Mtb–neutrophil interactions ill-defined. The phenotypic heterogeneity of neutrophils, and their propensity to engage in cellular cross-talk and to exert various functions during homeostasis and disease, have recently been reported, and such observations are newly emerging in TB. Here, we review the interactions of neutrophils with Mtb, including subcellular events and cell fate upon infection, and summarize the cross-talks between neutrophils and lung-residing and -recruited cells. We highlight the roles of neutrophils in TB pathophysiology, discussing recent findings from distinct models of pulmonary TB, and emphasize technical advances that could facilitate the discovery of novel neutrophil-related disease mechanisms and enrich our knowledge of TB pathogenesis.     

PHYSICS-BASED SIMULATION OF HIGH SPEED MACHINING

Computer simulation of high speed machining processes can provide a unique insight and reduce the number of design iterations required to advance and optimize the process. Predictive modeling of high speed machining of exotic materials has been hindered by the nonlinear behavior of this type of materials at extremely high strain, strain rate, and temperatures. This paper presents a physics-based modeling technology that includes the change in the material constitutive equation and the friction characterization at cutting speeds up to 400 m min^-1. The dependence of the accuracy of the predicted parameters, such as the chip formation on cutting forces, chip/tool/workpiece interface temperature, stress and strain distributions are also discussed. The fundamentals of metal cutting were utilized to understand the effect of parameter changes in regimes that are outside current empirical knowledge databases.     

Effects of Economic Pressure on Marital Conflict in Romania.

This study examined the interrelationships among economic pressure, maternal depression, social support, and marital conflict in a sample of 239 mothers in Romania. Data were collected through a school-based survey. Findings indicated that higher levels of economic pressure were associated with higher levels of marital conflict. Economic pressure was also associated with higher marital conflict indirectly through increased maternal depression and lowered social support. The present results were similar to those obtained in studies conducted among U.S. samples. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A new approach to predict ulcerative colitis activity through standard clinical–biological parameters using a robust neural network model

Neural Computing and Applications - Colonoscopy is the “gold” standard for evaluating disease activity in ulcerative colitis (UC). An important area of research is finding a...     

Design and implementation of a confidentiality and access control solution for publish/subscribe systems

The publish/subscribe model offers a loosely-coupled communication paradigm where applications interact indirectly and asynchronously. Publishers generate events that are sent to interested applications through a network of brokers. Subscribers express their interest by specifying filters that brokers can use for routing the events. Supporting confidentiality of messages being exchanged is still challenging. First of all, it is desirable that any scheme used for protecting the confidentiality of both the events and filters should not require publishers and subscribers to share secret keys. In fact, such a restriction is against the loose-coupling of the model. Moreover, such a scheme should not restrict the expressiveness of filters and should allow the broker to perform event filtering to route the events to the interested parties. Existing solutions do not fully address these issues. In this paper, we provide a novel scheme that supports (i) confidentiality for events and filters; (ii) allows publishers to express further constraints about who can access their events; (iii) filters that can express very complex constraints on events even if brokers are not able to access any information in clear on both events and filters; (iv) and, finally, it does not require publishers and subscribers to share keys. Furthermore, we show how we applied our scheme to a real-world e-health scenario, developed together with a hospital. We also describe the implementation of our solution in Java and the integration with an existing publish/subscribe system.     

Bead-based polymerase chain reaction on a microchip

We present a bead-based approach to microfluidic polymerase chain reaction (PCR), enabling fluorescent detection and sample conditioning in a single microchamber. Bead-based PCR, while not extensively investigated in microchip format, has been used in a variety of bioanalytical applications in recent years. We leverage the ability of bead-based PCR to accumulate fluorescent labels following DNA amplification to explore a novel DNA detection scheme on a microchip. The microchip uses an integrated microheater and temperature sensor for rapid control of thermal cycling temperatures, while the sample is held in a microchamber fabricated from (poly)dimethylsiloxane and coated with Parylene. The effects of key bead-based PCR parameters, including annealing temperature and concentration of microbeads in the reaction mixture, are studied to achieve optimized device sensitivity and detection time. The device is capable of detecting a synthetically prepared section of the Bordetella pertussis genome in as few as 10 temperature cycles with times as short as 15?min. We then demonstrate the use of the procedure in an integrated device; capturing, amplifying, detecting, and purifying template DNA in a single microfluidic chamber. These results show that this method is an effective method of DNA detection which is easily integrated in a microfluidic device to perform additional steps such as sample pre-conditioning.     

Interplay between Humoral and CLA+ T Cell Response against Candida albicans in Psoriasis

Candida albicans (CA) infections have been associated with psoriasis onset or disease flares. However, the integrated immune response against this fungus is still poorly characterized in psoriasis. We studied specific immunoglobulins in plasma and the CA response in cocultures of circulating memory CD45RA⁻ cutaneous lymphocyte antigen (CLA)^+/− T cell with autologous epidermal cells from plaque and guttate psoriasis patients (cohort 1, n = 52), and also healthy individuals (n = 17). A complete proteomic profile was also evaluated in plaque psoriasis patients (cohort 2, n = 114) regarding their anti-CA IgA levels. Increased anti-CA IgA and IgG levels are present in the plasma from plaque but not guttate psoriasis compared to healthy controls. CA cellular response is confined to CLA⁺ T cells and is primarily Th17. The levels of anti-CA IgA are directly associated with CLA⁺ Th17 response in plaque psoriasis. Proteomic analysis revealed distinct profiles in psoriasis patients with high anti-CA IgA. C-C motif chemokine ligand 18, chitinase-3-like protein 1 and azurocidin were significantly elevated in the plasma from plaque psoriasis patients with high anti-CA levels and severe disease. Our results indicate a mechanism by which Candida albicans exposure can trigger a clinically relevant IL-17 response in psoriasis. Assessing anti-CA IgA levels may be useful in order to evaluate chronic psoriasis patients.     

Miscibility and properties of linear poly(l-lactide)/branched poly(l-lactide) copolyester blends

Polymer blends consisting of linear poly(l-lactide) (PLLA) and different proportions of dendritic PLLA-based copolyesters (hb-PLLA) characterized by different degrees of branching (DB) were obtained in melt. The solid-state properties of poly(l-lactide)s and their blends were investigated by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), atomic force microscopy (AFM) and stress-strain measurements. DSC and DMA methods proved miscibility of PLLA/hb-PLLA blends for the studied composition range. AFM indicated that no phase separation occurs in PLLA/hb-PLLA blends and that PLLA and hb-PLLA cocrystallize in one single lamellae type. The mechanical characteristics of PLLA/hb-PLLA blends deteriorated with an increase of the DB and with changing blend composition. Susceptibility of the blends to biodegradation was studied by measuring the weight loss in two different biodegradation media. PLLA/hb-PLLA blends showed more pronounced hydrophilic character and higher susceptibility to biodegradation with an increase in the degree of branching.     

Evaluation of hydrogen bonding ability of liquids and solids by C-13 NMR. Silica gel as a strong hydrogen bond donor

The chemical shift difference between signals of C() and C() of unsaturated ketones, , which we used before to measure acid strengths, has now been used to evaluate the hydrogen bond donor ability of solvents which are not acidic enough to hydronate the indicator. For such solvents there is no general correlation between H-bond donor ability and acid strength: hexa-fluoroisopropanol is a much weaker acid than acetic acid, but it is a stronger H-bond donor. The method can be applied to evaluate the H-bonding properties of solid surfaces, and it was thus found that silica gel has a much stronger H-bond donor ability than methanol or acetic acid.